title: Cytomegalovirus-based cancer vaccines expressing TRP2 induce rejection of melanoma in mice.
abstract: Cytomegalovirus (CMV) induces strong and long-lasting immune responses, which make it an attractive candidate for a cancer vaccine vector. In this study, we tested whether a tumor antigen expressed in CMV can induce a strong anti-tumor effect. We expressed an unmodified melanoma antigen, mouse tyrosinase-related protein 2 (TRP2), in mouse cytomegalovirus (MCMV). Prophylactic vaccination of the mice with a single dose of MCMV-TRP2 induced rejection of B16 melanoma challenge; therapeutic vaccination with MCMV-TRP2 prolonged the survival of the mice challenged with B16 cells. Additionally, vaccination with MCMV-TRP2 five months before tumor challenge still induced tumor rejection, which indicated that the vaccine induced long-term protection. Furthermore, MCMV-TRP2 protected mice against B16 melanoma challenge regardless of the pre-existing CMV infection. We found that vaccination with MCMV-TRP2 induced long-lasting TRP2 specific antibodies but not CD8 T cells. In addition, depletion of CD4 and CD8 T cells did not compromise the antitumor effect by MCMV-TRP2; while in B cell deficient (μMT) mice, the vaccine lost its antitumor effect. These results indicate that antibodies, not T cells, are important in mediating the antitumor effect during the effector phase by the vaccine. We also made a spread deficient MCMV-TRP2 lacking the essential glycoprotein gL, which showed a similar antitumor effect. In conclusion, our study indicates that tumor antigen (TRP2) expressed in MCMV induces a strong and long-lasting anti-melanoma effect through an antibody-dependent mechanism. Our findings demonstrate that CMV might be a promising vector for the development of cancer vaccines.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA. xu@ohsu.edu
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Tameka
authors.initials: T
authors.lastname: Smith
authors.forename: Finn
authors.initials: F
authors.lastname: Grey
authors.forename: Ann B
authors.initials: AB
authors.lastname: Hill
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D019496:Cancer Vaccines; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
keywords: Cancer vaccine; Cytomegalovirus; Melanoma; Tyrosinase related protein 2